Project Summary/Abstract African American women have 1.5 times the rates of preterm birth (PTB) (<37 weeks completed gestation) compared with non-Hispanic white women. This disproportionately high PTB rate in African Americans is a persistent health inequity that leads to high child mortality, morbidity, and developmental delays. Neighborhood disorder (e.g., abandoned buildings) has been related to psychological distress and risk for PTB. Higher levels of psychological distress and increased risk of PTB have been related to epigenetic modifications, and specifically to DNA methylation of stress-related glucocorticoid (GC) genes. However, no published study has examined the relationship between neighborhood disorder, psychological distress, DNA methylation of GC genes, and PTB in general or within the highest risk group among U.S. women ? African Americans. The purpose of this study is to examine the relationships among neighborhood disorder, psychological distress, DNA methylation of candidate GC genes, and gestational age at birth in African American women. In this prospective cohort study, I will analyze data from 100 pregnant African American women among all participants enrolled in the NIH R01 study Social stressors and inflammation: A mixed methods approach to preterm birth (7R01MD001575-02, PI Giurgescu, sponsor). The nested subsample will be selected among those women from the parent study who had a spontaneous birth (preterm or term) to ensure a homogenous sample for DNA methylation after all data and specimens are collected. Questionnaire data about neighborhood disorder and psychological distress, maternal blood drawn at 14-16 weeks gestation, and birth data will be available from the parent study. We will analyze maternal leukocytes for differential DNA methylation in six GC candidate genes (AVP, CRH, CRHBP, HSD11B2, NR3C1, and FKBP5). I aim to: (1) Examine the relationship between neighborhood disorder and maternal leukocyte DNA methylation of GC candidate genes; (2) Examine the relationship between maternal leukocyte DNA methylation of GC candidate genes and gestational age at birth; and (3) Explore the relationships among neighborhood disorder, psychological distress, differential DNA methylation in GC candidate genes and gestational age at birth. The proposed training plan will provide numerous opportunities for development of skills encompassing recruitment of participants, data collection, laboratory and biostatistical training as well as grantsmanship development and dissertation research findings dissemination. The proposed research is highly relevant to NIH's mission to elucidate mechanisms underlying health disparities in PTB and incorporating epigenomic technology into nursing research and practice. This study will advance scientific understanding of the biologic effects of the neighborhood environment on PTB for African American women.